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Detrimental role for CCAAT/enhancer binding protein δ in blood-borne brain infection
JanWillem Duitman1, Mercedes Valls Serón2,3, JooYeon Engelen-Lee2,3
1Center for Experimental and Molecular Medicine (CEMM) Academic Medical Center, University of Amsterdam, P.O. Box 22660, 1100DD, Amsterdam, The Netherlands. j.w.duitman@amc.uva.nl.
Background:
The most frequent pathogen that causes bacterial meningitis is the Gram-positive bacterium Streptococcus (S.) pneumoniae. CCAAT/enhancer binding protein δ is a transcription factor that has recently been hypothesized to play a detrimental role in outcome of meningitis caused by S. pneumoniae. Here, we studied the role of C/EBPδ prior to the development of pneumococcal meningitis.
Methods:
Wild-type and C/EBPδ-deficient mice (C/EBPδ-/-) were intraveneously infected with S. pneumoniae and sacrificed after 24 or 48 h. cebpδ expression, bacterial loads, inflammatory response and pathology in the brain were assessed.
Results:
S. pneumoniae induces cebpδ expression in the brain during blood-borne brain infection. In comparison to wild-type mice, C/EBPδ-/- animals showed decreased bacterial loads in blood and brain 48 h after inoculation. In the blood compartment, the host inflammatory response was significantly lower upon infection in C/EBPδ-/- mice as compared to wild-type mice.
Conclusion:
C/EBPδ facilitates bacterial dissemination to the brain and enhances the immune response in the blood compartment. Our study suggests that C/EBPδ plays a detrimental role during the initial development of blood-borne brain infection.
Insights
CCAAT/enhancer binding protein delta (C/EBPδ) aids Streptococcus pneumoniae spread and immune response in meningitis. Eliminating C/EBPδ in mice reduced bacterial load and inflammation, suggesting a detrimental role in early infection.
Area of Science:
- Neuroscience
- Infectious Disease Research
- Molecular Biology
Background:
- * Streptococcus pneumoniae is a leading cause of bacterial meningitis.
- * CCAAT/enhancer binding protein delta (C/EBPδ) is a transcription factor potentially involved in meningitis outcomes.
- * The role of C/EBPδ in the early stages of pneumococcal meningitis requires further investigation.
Purpose of the Study:
- * To investigate the role of C/EBPδ in the initial development of Streptococcus pneumoniae-induced meningitis.
- * To assess the impact of C/EBPδ deficiency on bacterial dissemination and host inflammatory response.
Main Methods:
- * Intravenous infection of wild-type and C/EBPδ-deficient (C/EBPδ-/-) mice with Streptococcus pneumoniae.
- * Assessment of C/EBPδ expression, bacterial loads, inflammatory markers, and brain pathology at 24 and 48 hours post-infection.
Main Results:
- * Streptococcus pneumoniae infection induces C/EBPδ expression in the brain.
- * C/EBPδ-/- mice exhibited reduced bacterial loads in blood and brain at 48 hours.
- * Host inflammatory response in the blood was significantly lower in C/EBPδ-/- mice compared to wild-type.
Conclusions:
- * C/EBPδ promotes bacterial spread to the brain during pneumococcal meningitis.
- * C/EBPδ enhances the host's immune response in the blood compartment.
- * C/EBPδ plays a detrimental role in the early phase of blood-borne pneumococcal brain infection.
